To the Editor: The recent Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) article by Michael J. Ostacher, M.D., M.P.H., et al. (ajp0367r1), published in the March 2010 issue of the Journal, identified an association between current or past substance abuse or dependence in bipolar disorder patients and a greater likelihood for affective polarity switch from depression to mania, hypomania, or mixed state relative to when comorbid substance use disorders were absent (1). Consistent with this finding, previous naturalistic data from a study that I co-authored (2) demonstrated that a history of comorbid alcohol or substance use disorders conferred an approximate 7-fold increased risk in bipolar disorder patients for developing antidepressant-induced mania, regardless of cotherapy with antimanic agents. Using multiple regression, similar findings during antidepressant therapy were reported by Manwani et al. (3). In light of this prior literature, it would have been informative within the STEP-BD database to determine whether the presence or absence of antidepressant use mediated the relationship between a comorbid substance use disorder and affective polarity switch from depression. Although STEP-BD subjects with comorbid substance use disorders were less likely to receive an antidepressant than those without substance use disorders, this comparison in itself does not address the question of whether depressed bipolar subjects with a substance use disorder were more likely to experience a polarity switch in the presence rather than absence of an adjunctive antidepressant.